nsalomonis / altanalyze

AltAnalyze is a multi-functional and easy-to-use software package for automated single-cell and bulk gene and splicing analyses. Easy-to-use precompiled graphical user-interface versions available from our website.
http://www.altanalyze.org
Apache License 2.0
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Changes to ASPIRE p-value calculation #7

Closed GoogleCodeExporter closed 9 years ago

GoogleCodeExporter commented 9 years ago
Background
In version 1.16 beta of AltAnalyze, we introduced the ASPIRE p-value as the 
default metric for assessing reproducibility of ASPIRE scores for reciprocal 
junction analysis of HJAY, MJAY and AltMouse arrays. Previously, the 
appropriate recommended metric was the permutation p-value (still optional). An 
issue with the permutation p-value is that it's power is dependent on the 
number of possible permutation that result from the number of replicates.

The ASPIRE p-value was designed as an optional replacement for the permutation 
p-value. This algorithm calculates and stores an ASPIRE scores for each 
experimental sample for the two reciprocal probesets (normalized baseline 
expression and normalized experimental expression), versus the mean normalized 
baseline expression for all baseline samples (normalized baseline sample values 
treated as experimental in the ASPIRE equation). These p-values are stored in 
two different lists (baseline replicates versus baseline average and 
experimental replicates versus baseline average). A one-way ANOVA p-value is 
calculated between these two lists to derive the ASPIRE p-value. 

Updates
While initially, this p-value seemed appropriate replacement, the baseline 
replicate comparisons appear too variable when a small number of replicates is 
present. Thus, we changed this metric as follows:
Normalized baseline replicate values are now compared to the mean normalized 
experimental replicate values. Here, the baseline replicates are treated as 
experimental and the experimental mean is treated as baseline in the ASPIRE 
equation. 

As before, experimental replicate values are compared to the baseline mean and 
the two resulting replicate ASPIRE score lists are compared by one-way ANOVA. 
Preliminary analysis of RNASeq data (version 2.0) where only two replicates are 
present seems to indicate this is a reasonable measure of variability. 
Nonetheless, we recommend using the FDR adjustment of this p-value, present in 
the results file, as an additional filter.

Original issue reported on code.google.com by nsalomo...@gmail.com on 5 Feb 2011 at 6:52